A promoter is a DNA signal for starting mRNA synthesis (transcription) with DNA as a template. The promoter has a role in determining the efficiency of transcription.
One of the first hosts used for the production of desired physiologically active substances by means of recombinant DNA technology was Escherichia coli as the host. Shortly thereafter, microorganisms such as Saccharomyces cerevisiae and Bacillus subtilis joined the class of hosts in frequent use because of the ease with which they can be cultured and of the advancement resulting from the study of host-vector systems. (cf. Goeddel, D. V., Itakura, K. et al., Proc. Natl. Acad. Sci. USA, 76, 106 (1979) and Nagata, S., Taira, S. H. and Weissmann, C., Nature, 284, 1316 (1980)).
Recently, to produce macromolecular glycoproteins in a form similar to their naturally occurring form and at the same time in a soluble form by means of recombinant DNA technology, interest has been drawn to expression systems in which animal cells are used as hosts.
The development of promoters for gene expression in animal cells, however, has been slow and, at present, only the SV40 promoter, metallothionein promoter and a few others are known.
CSF-1, one of many colony stimulating factors acts on and promotes the differentiation and proliferation of human macrophages.
In recent years, new information on the base sequence of cDNA coding for CSF-1 has been collected by using genetic engineering techniques (WO 86/04607; Kawasaki et al; Science, 230, 291-296 (1985), Ladner, et al., EMBO Journal, 6, 2693-2698 (1987) and Wong, et al., Science, 235, 1504-1508 (1987)).
Based on the above findings, the present inventors directed their attention to the CSF-1 gene in their attempt to develop a promoter for expression in animal cells.
As a result of intensive investigation in search of a novel promoter, the promoter region upstream from the 5' end of the human CSF-1 gene was analyzed and the results therefrom are presented herein.